The applicant seeks renewal of a K24 Mid-Career Investigator Award in patient-oriented research in order to continue to develop his career as a clinical researcher and to devote the effort and time necessary for the mentoring of young clinical researchers. During the initial 4 years of funding the applicant has been highly successful, both as a mentor and as a researcher. The application describes his established research and mentoring program and plans to continue those endeavors. The mentoring plan sets out 10 key areas around which the mentoring of every trainee is structured. These are: i) Ethical responsibilities and scientific integrity; ii) Research of background information; iii) Formulating a hypothesis; iv) Design and performance of an experiment; v) Data organization, storage and analysis; vi) Writing a paper; vii) Presenting findings at a meeting; viii) Reviewing the work of others; ix) Grant writing and x) Planning a career. The applicant describes how his individual resources, and those of the institution, are applied in order to assure a successful and productive training program. The applicant has an active, funded research program and devotes 80% of his time to clinical research. Institutional letters of support outline the applicant's scientific achievements, his contributions as a teacher and mentor, the outstanding intellectual and physical resources available to him, and that, if funded, he will be provided with continued protected time to perform research and mentor trainees. The overall goal of the investigator's research program is to define the genetic and non-genetic factors that determine the variability in human vascular response. One of several active research programs is described. This project, Genetic Basis of Altered Sensitivity to beta1-Adrenoceptor Antagonists, is funded through a Pharmacogenetics and Pharmacogenomics Knowledge Base (Pharm GKB) grant and builds on the applicant's previous work. It will test the overall hypothesis that variable sensitivity to beta-blockers is a result of genetic variability in the beta1-AR. The renewal of a K24 award will allow the investigator to continue to pursue a highly productive career as a patient-oriented researcher and mentor. The unique research environment, his established ongoing research program and commitment to mentoring will allow him to continue to contribute to the fostering of clinical research through the hands-on training of young investigators.